Biguanides, including polymeric biguanides, as a class are known to have antimicrobial activity. Poly(hexamethylene biguanide) also known as PHMB or PAPB has been used as an antimicrobial component in many applications including topical disinfectants and as a preservative in health care products. PHMB is commonly represented by the following formula, though it is known to exist as a complex mixture of polymeric biguanides with various terminal groups including guanidine (not shown).
The value n represents the number of repeating units of the biguanide polymer. GB 1434040 describes the use of PHMB and several other biguanide structures and their effectiveness as antimicrobial components.
PHMB has been used in ophthalmic compositions, e.g., in contact, lens care solutions. Ophthalmic lens care solutions that contain PHMB represent a significant improvement in patient comfort and antimicrobial effectiveness compared to most other antimicrobial components. However, as with any antimicrobial component there remains a tradeoff between the concentration of the antimicrobial component in the solution and the comfort experienced by the patient. Due to its wide commercial acceptance, extensive efforts have been made to improve the antimicrobial efficacy or the comfort level to the patient by chemically modifying PHMB. For example, many derivatives of PHMB have been reported that alter the length of the alkylene group, place substituents on the alkylene repeating unit, change the length of the polymer, i.e., molecular weight or n, or modify the terminal groups.
EP701821 describes a biguanide derivative having 1 to 500 polymeric repeat units that is formulated with a phosphoric acid and phosphoric acid salt. EP788797 describes the use of PHMB having a molecular weight of less than 5000 Da, e.g., 3000 Da to 4000 Da for treatment of urogenital disease and parasites of the abdominal cavity.
U.S. Pat. No. 6,121,327 describes a PHMB derivative in which the amino terminal groups are replaced by amido groups, RC(O)NH—. The R group can include alkyls, cycloalkyls, polyethyleneoxides and polypropyleneoxides. In the case of poly(ethyl)propylene oxides, the added surfactant character is said to provide good efficacy and lower toxicity.
There remains an interest and need for an improved antimicrobial biguanide composition that offers a greater comfort level to the patient without sacrificing antimicrobial efficacy.